59.4 Folate:B12

59.4.1 Global tests

Type III ANOVA on main and interaction effects, and LM model summaries.

Prolactin

	Chisq	Df	Pr(>Chisq)
(Intercept)	169.8724552	1	<0.0001	***
folate_B12	3.7847549	1	0.05	ns
GDM_new	0.5764352	1	0.4	ns
Study	2.6871647	1	0.1	ns
GA_samp	151.7582805	1	<0.0001	***
folate_B12:GDM_new	0.0111970	1	0.9	ns
GDM_new:Study	1.1101316	1	0.3	ns
folate_B12:Study	5.7254015	1	0.02	*
folate_B12:GDM_new:Study	0.0207807	1	0.9	ns

HPL

	Chisq	Df	Pr(>Chisq)
(Intercept)	37.8071254	1	<0.0001	***
folate_B12	0.0821847	1	0.8	ns
GDM_new	0.5570061	1	0.5	ns
Study	9.9200537	1	0.002	**
GA_samp	1959.9141332	1	<0.0001	***
folate_B12:GDM_new	5.6137682	1	0.02	*
GDM_new:Study	1.5557746	1	0.2	ns
folate_B12:Study	0.0319745	1	0.9	ns
folate_B12:GDM_new:Study	5.9889500	1	0.01	*

GH2

	Chisq	Df	Pr(>Chisq)
(Intercept)	325.1881724	1	<0.0001	***
folate_B12	1.0321016	1	0.3	ns
GDM_new	0.0016102	1	1.0	ns
Study	0.1084480	1	0.7	ns
GA_samp	877.5072246	1	<0.0001	***
folate_B12:GDM_new	2.4568213	1	0.1	ns
GDM_new:Study	0.0027551	1	1.0	ns
folate_B12:Study	0.0171659	1	0.9	ns
folate_B12:GDM_new:Study	2.8020725	1	0.09	ns

Insulin

	model term	df1	df2	F.ratio	Chisq	p.value
1	folate_B12	1	Inf	0.344	0.344	0.6	ns
5	GDM_new	1	Inf	28.664	28.664	<0.0001	***
7	Study	1	Inf	8.069	8.069	0.005	**
8	GA_samp	1	Inf	0.082	0.082	0.8	ns
2	folate_B12:GDM_new	1	Inf	0.000	0.000	1.0	ns
4	folate_B12:Study	1	Inf	0.038	0.038	0.8	ns
6	GDM_new:Study	1	Inf	0.602	0.602	0.4	ns
3	folate_B12:GDM_new:Study	1	Inf	0.282	0.282	0.6	ns

HOMA.IR

	model term	df1	df2	F.ratio	Chisq	p.value
1	folate_B12	1	Inf	0.646	0.646	0.4	ns
5	GDM_new	1	Inf	29.220	29.220	<0.0001	***
7	Study	1	Inf	14.790	14.790	0.0001	***
8	GA_samp	1	Inf	0.003	0.003	1.0	ns
2	folate_B12:GDM_new	1	Inf	0.057	0.057	0.8	ns
4	folate_B12:Study	1	Inf	0.000	0.000	1.0	ns
6	GDM_new:Study	1	Inf	0.886	0.886	0.3	ns
3	folate_B12:GDM_new:Study	1	Inf	0.162	0.162	0.7	ns

GLUC3_mmol.L

	model term	df1	df2	F.ratio	Chisq	p.value
1	folate_B12	1	Inf	0.869	0.869	0.4	ns
5	GDM_new	1	Inf	5.757	5.757	0.02	*
7	Study	1	Inf	25.701	25.701	<0.0001	***
8	GA_samp	1	Inf	0.401	0.401	0.5	ns
2	folate_B12:GDM_new	1	Inf	1.596	1.596	0.2	ns
4	folate_B12:Study	1	Inf	0.626	0.626	0.4	ns
6	GDM_new:Study	1	Inf	1.077	1.077	0.3	ns
3	folate_B12:GDM_new:Study	1	Inf	0.045	0.045	0.8	ns

59.4.2 Model summary

Ratio of Geometric means (95% CI)

Prolactin

Var	Effect	P
(Intercept)	2.69 (2.29, 3.09)	<0.0001
folate_B12	-0.00 (-0.00, -0.00)	0.04
GDM_newGDM	-0.11 (-0.34, 0.13)	0.37
StudySTOP	-0.13 (-0.29, 0.02)	0.10
GA_samp	0.15 (0.13, 0.17)	<0.0001
folate_B12:GDM_newGDM	-0.00 (-0.00, 0.00)	0.95
GDM_newGDM:StudySTOP	0.17 (-0.06, 0.40)	0.15
folate_B12:StudySTOP	0.00 (0.00, 0.00)	0.01

HPL

Var	Effect	P
(Intercept)	0.66 (0.45, 0.87)	<0.0001
folate_B12	-0.00 (-0.00, 0.00)	0.77
GDM_newGDM	0.06 (-0.10, 0.22)	0.46
StudySTOP	0.14 (0.05, 0.22)	0.002
GA_samp	0.29 (0.28, 0.30)	<0.0001
folate_B12:GDM_newGDM	-0.00 (-0.00, -0.00)	0.02
GDM_newGDM:StudySTOP	-0.11 (-0.29, 0.06)	0.21
folate_B12:StudySTOP	-0.00 (-0.00, 0.00)	0.86
folate_B12:GDM_newGDM:StudySTOP	0.00 (0.00, 0.00)	0.01

GH2

Var	Effect	P
(Intercept)	-2.55 (-2.82, -2.27)	<0.0001
folate_B12	-0.00 (-0.00, 0.00)	0.10
GDM_newGDM	-0.14 (-0.31, 0.03)	0.11
StudySTOP	-0.04 (-0.15, 0.07)	0.43
GA_samp	0.26 (0.24, 0.28)	<0.0001
folate_B12:GDM_newGDM	-0.00 (-0.00, 0.00)	0.89
GDM_newGDM:StudySTOP	0.17 (0.00, 0.34)	0.05
folate_B12:StudySTOP	0.00 (-0.00, 0.00)	0.37

Insulin

Var	Effect	P
(Intercept)	2.60 (2.07, 3.13)	<0.0001
folate_B12	-0.00 (-0.00, 0.00)	0.66
GDM_newGDM	0.84 (0.50, 1.19)	<0.0001
StudySTOP	-0.31 (-0.52, -0.10)	0.004
GA_samp	0.00 (-0.03, 0.04)	0.77
folate_B12:GDM_newGDM	-0.00 (-0.00, 0.00)	0.72
GDM_newGDM:StudySTOP	-0.27 (-0.61, 0.07)	0.12
folate_B12:StudySTOP	0.00 (-0.00, 0.00)	0.88

HOMA.IR

Var	Effect	P
(Intercept)	1.24 (0.68, 1.81)	<0.0001
folate_B12	-0.00 (-0.00, 0.00)	0.56
GDM_newGDM	0.95 (0.57, 1.33)	<0.0001
StudySTOP	-0.47 (-0.69, -0.25)	<0.0001
GA_samp	0.00 (-0.03, 0.04)	0.96
folate_B12:GDM_newGDM	-0.00 (-0.00, 0.00)	0.58
GDM_newGDM:StudySTOP	-0.33 (-0.71, 0.04)	0.08
folate_B12:StudySTOP	0.00 (-0.00, 0.00)	0.75

GLUC3_mmol.L

Var	Effect	P
(Intercept)	1.73 (1.61, 1.84)	<0.0001
folate_B12	-0.00 (-0.00, 0.00)	0.64
GDM_newGDM	0.15 (0.01, 0.28)	0.03
StudySTOP	-0.16 (-0.20, -0.11)	<0.0001
GA_samp	-0.00 (-0.01, 0.00)	0.53
folate_B12:GDM_newGDM	-0.00 (-0.00, 0.00)	0.15
GDM_newGDM:StudySTOP	-0.08 (-0.20, 0.04)	0.17
folate_B12:StudySTOP	0.00 (-0.00, 0.00)	0.28

59.4.3 Estimated means

Estimated marginal means (or adjusted means) adjusted for GA at sampling.

Results are averaged over the levels of Folate:B12 ratio and may be misleading when interaction term is involved.

Prolactin

Study	GDM_new	response	SE	df	lower.CL	upper.CL
SCOPE	Uncomplicated	94.29984	7.625504	102.8302	80.32660	110.7038
STOP	Uncomplicated	93.42616	6.988326	75.6675	80.49400	108.4360
SCOPE	GDM	84.46162	10.602255	465.7427	65.99816	108.0904
STOP	GDM	98.93897	8.704386	140.0553	83.14349	117.7353

HPL

Study	GDM_new	response	SE	df	lower.CL	upper.CL
SCOPE	Uncomplicated	86.17832	2.538979	188.2151	81.31257	91.33523
STOP	Uncomplicated	98.38177	2.495652	104.5259	93.55549	103.45702
SCOPE	GDM	80.17900	4.471729	630.3602	71.86149	89.45920
STOP	GDM	95.49611	3.390919	309.2910	89.05168	102.40691

GH2

Study	GDM_new	response	SE	df	lower.CL	upper.CL
SCOPE	Uncomplicated	2.239282	0.0748675	442.0255	2.096872	2.391365
STOP	Uncomplicated	2.209041	0.0576251	202.4688	2.098291	2.325636
SCOPE	GDM	1.942566	0.1508117	1034.7015	1.668073	2.262228
STOP	GDM	2.269315	0.0938631	485.5939	2.092182	2.461444

Insulin

Study	GDM_new	response	SE	df	asymp.LCL	asymp.UCL
SCOPE	Uncomplicated	14.07586	0.8800801	Inf	12.452432	15.91092
STOP	Uncomplicated	10.44075	0.4305347	Inf	9.630115	11.31962
SCOPE	GDM	32.03042	4.9978966	Inf	23.590902	43.48912
STOP	GDM	18.08465	1.3890691	Inf	15.557147	21.02279

HOMA.IR

Study	GDM_new	response	SE	df	asymp.LCL	asymp.UCL
SCOPE	Uncomplicated	3.413043	0.2271328	Inf	2.995681	3.888552
STOP	Uncomplicated	2.175776	0.0942232	Inf	1.998722	2.368514
SCOPE	GDM	8.531524	1.4624141	Inf	6.097048	11.938056
STOP	GDM	3.899323	0.3220337	Inf	3.316583	4.584452

GLUC3_mmol.L

Study	GDM_new	response	SE	df	asymp.LCL	asymp.UCL
SCOPE	Uncomplicated	5.428502	0.0689608	Inf	5.295011	5.565360
STOP	Uncomplicated	4.713930	0.0424742	Inf	4.631413	4.797917
SCOPE	GDM	6.085856	0.3238477	Inf	5.483105	6.754867
STOP	GDM	4.878311	0.0637282	Inf	4.754991	5.004829

59.4.4 Comparisons

59.4.4.1 Within Groups

Effect for every 100 unit increase in Folate:B12 ratio.

Hormone	Contrast	Study	GDM_new	Ratio of Geometric means (95% CI)	P-value
Prolactin	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.961 (0.924, 0.999)	0.04
Prolactin	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	1.023 (0.991, 1.055)	0.2
Prolactin	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.959 (0.906, 1.016)	0.2
Prolactin	folate_B12245.96 / folate_B12145.96	STOP	GDM	1.021 (0.980, 1.064)	0.3
HPL	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.997 (0.976, 1.018)	0.8
HPL	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	0.994 (0.977, 1.012)	0.5
HPL	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.932 (0.885, 0.981)	0.008
HPL	folate_B12245.96 / folate_B12145.96	STOP	GDM	1.006 (0.982, 1.030)	0.6
GH2	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.977 (0.950, 1.005)	0.1
GH2	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	0.993 (0.970, 1.016)	0.5
GH2	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.974 (0.934, 1.016)	0.2
GH2	folate_B12245.96 / folate_B12145.96	STOP	GDM	0.990 (0.960, 1.020)	0.5
Insulin	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.990 (0.944, 1.037)	0.7
Insulin	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	0.994 (0.960, 1.029)	0.7
Insulin	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.979 (0.918, 1.045)	0.5
Insulin	folate_B12245.96 / folate_B12145.96	STOP	GDM	0.983 (0.935, 1.035)	0.5
HOMA.IR	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.985 (0.938, 1.035)	0.6
HOMA.IR	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	0.995 (0.958, 1.033)	0.8
HOMA.IR	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.968 (0.901, 1.040)	0.4
HOMA.IR	folate_B12245.96 / folate_B12145.96	STOP	GDM	0.977 (0.925, 1.033)	0.4
GLUC3_mmol.L	folate_B12245.96 / folate_B12145.96	SCOPE	Uncomplicated	0.998 (0.988, 1.007)	0.6
GLUC3_mmol.L	folate_B12245.96 / folate_B12145.96	STOP	Uncomplicated	1.007 (0.995, 1.018)	0.2
GLUC3_mmol.L	folate_B12245.96 / folate_B12145.96	SCOPE	GDM	0.982 (0.956, 1.009)	0.2
GLUC3_mmol.L	folate_B12245.96 / folate_B12145.96	STOP	GDM	0.991 (0.976, 1.006)	0.2

59.4.4.2 Between Groups

Below are comparisons of the differences in the change in Folate:B12 ratio between groups. I.e. whether the change in Folate:B12 ratio are different between groups.

Prolactin

contrast	ratio	SE	df	lower.CL	upper.CL	p.value
SCOPE/SCOPE (Overall)	1.1331947	0.0552608	1362.154	1.0298130	1.246955	0.010	*
STOP/SCOPE (Uncomplicated)	1.0645162	0.0259558	1362.154	1.0147970	1.116671	0.010	*
STOP/SCOPE (GDM)	1.0645162	0.0259558	1362.154	1.0147970	1.116671	0.010	*
GDM/Uncomplicated (SCOPE)	0.9985844	0.0250522	1343.765	0.9506285	1.048960	0.955	ns
GDM/Uncomplicated (STOP)	0.9985844	0.0250522	1343.765	0.9506285	1.048960	0.955	ns

HPL

contrast	ratio	SE	df	lower.CL	upper.CL	p.value
SCOPE/SCOPE (Overall)	1.0762540	0.0345865	649.9090	1.0104376	1.1463574	0.023	*
STOP/SCOPE (Uncomplicated)	0.9974815	0.0140667	1289.1463	0.9702636	1.0254629	0.858	ns
STOP/SCOPE (GDM)	1.0789714	0.0311288	549.2789	1.0195256	1.1418832	0.009	**
GDM/Uncomplicated (SCOPE)	0.9349310	0.0265494	504.3811	0.8841983	0.9885745	0.018	*
GDM/Uncomplicated (STOP)	1.0113108	0.0153519	1398.9582	0.9816395	1.0418789	0.459	ns

GH2

contrast	ratio	SE	df	lower.CL	upper.CL	p.value
SCOPE/SCOPE (Overall)	1.0319994	0.0364042	1360.679	0.9630000	1.105943	0.372	ns
STOP/SCOPE (Uncomplicated)	1.0158737	0.0179177	1360.679	0.9813256	1.051638	0.372	ns
STOP/SCOPE (GDM)	1.0158737	0.0179177	1360.679	0.9813256	1.051638	0.372	ns
GDM/Uncomplicated (SCOPE)	0.9973472	0.0184678	1391.902	0.9617694	1.034241	0.886	ns
GDM/Uncomplicated (STOP)	0.9973472	0.0184678	1391.902	0.9617694	1.034241	0.886	ns

Insulin

contrast	ratio	SE	df	asymp.LCL	asymp.UCL	p.value
SCOPE/SCOPE (Overall)	1.0087364	0.0565249	Inf	0.9038166	1.125836	0.877	ns
STOP/SCOPE (Uncomplicated)	1.0043587	0.0281398	Inf	0.9506927	1.061054	0.877	ns
STOP/SCOPE (GDM)	1.0043587	0.0281398	Inf	0.9506927	1.061054	0.877	ns
GDM/Uncomplicated (SCOPE)	0.9894412	0.0289828	Inf	0.9342358	1.047909	0.717	ns
GDM/Uncomplicated (STOP)	0.9894412	0.0289828	Inf	0.9342358	1.047909	0.717	ns

HOMA.IR

contrast	ratio	SE	df	asymp.LCL	asymp.UCL	p.value
SCOPE/SCOPE (Overall)	1.0197048	0.0615394	Inf	0.9059501	1.147743	0.746	ns
STOP/SCOPE (Uncomplicated)	1.0098043	0.0304709	Inf	0.9518141	1.071328	0.746	ns
STOP/SCOPE (GDM)	1.0098043	0.0304709	Inf	0.9518141	1.071328	0.746	ns
GDM/Uncomplicated (SCOPE)	0.9823047	0.0316369	Inf	0.9222141	1.046311	0.579	ns
GDM/Uncomplicated (STOP)	0.9823047	0.0316369	Inf	0.9222141	1.046311	0.579	ns

GLUC3_mmol.L

contrast	ratio	SE	df	asymp.LCL	asymp.UCL	p.value
SCOPE/SCOPE (Overall)	1.0177933	0.0165485	Inf	0.9858703	1.050750	0.278	ns
STOP/SCOPE (Uncomplicated)	1.0088574	0.0082016	Inf	0.9929100	1.025061	0.278	ns
STOP/SCOPE (GDM)	1.0088574	0.0082016	Inf	0.9929100	1.025061	0.278	ns
GDM/Uncomplicated (SCOPE)	0.9844365	0.0108104	Inf	0.9634748	1.005854	0.153	ns
GDM/Uncomplicated (STOP)	0.9844365	0.0108104	Inf	0.9634748	1.005854	0.153	ns

59.4.5 Diagnostics

Model diagnositcs.

Diagnositcs for PRL (ng/ml)

Diagnositcs for hPL (μg/ml)

Diagnositcs for GH2 (ng/ml)

Diagnositcs for Insulin (uU/ml)

Diagnositcs for HOMA-IR

Diagnositcs for Glucose (mmol/L)

59.4.6 Plots